A Study of N-Acetylcysteine (N-AC)in People Receiving CAR T-cell Therapy for Lymphoma

Phase I Study of N-Acetylcysteine to Optimize Metabolic Tumor Microenvironment in CD19 CAR T-cell Therapy in Lymphoma

The purpose of this study is to test the safety of N-AC when given in combination with Yescarta to people with lymphoma. This study will test different doses of N-AC to find the highest dose that causes few or mild side effects in participants.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gunjan Shah, MD; Phone Number: 646-608-3734; Email: shahg@mskcc.org
• Study Contact Backup: Name: Alison Moskowitz, MD; Phone Number: 646-608-3726

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Gunjan Shah, MD; Phone Number: 646-608-3734

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be 18 years of age or older
• Patients who will receive axicabtagene ciloleucel for treatment of lymphoma

• Patients must have adequate end organ function to be eligible for this study as defined by the following criteria:

  • ECOG performance status 0-2
  • Hematologic function with ANC ≥ 1000, Hgb ≥ 8, Plt ≥ 50k unless there is disease related hematologic toxicity
  • Renal function with CrCr ≥ 40 ml/min or Cr ≤ 1.5 x ULN
  • Hepatic function with ALT/AST ≤ 2.5 x ULN, TBili ≤ 1.5 x ULN.

Exclusion Criteria:

• Patients with known allergy to N-AC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Lymphoma, Cohort 1; The first dose escalation cohort in the study will be treated at 25% of that target dose level	Drug: N-Acetylcysteine; N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.; Other Names: N-AC
Experimental: Participants with Lymphoma, Cohort 2; The second cohort in the study will be treated at 50% of that target dose level	Drug: N-Acetylcysteine; N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.; Other Names: N-AC
Experimental: Participants with Lymphoma, Cohort 3; The third cohort in the study will be treated at 100% of that target dose level only if no DLTs are seen at lower doses.	Drug: N-Acetylcysteine; N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.; Other Names: N-AC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of N-AC	This is a phase 1 dose escalation and expansion study to determine the maximum tolerated dose and recommended phase 2 dose of NAC given in conjunction with axicabtagene ciloleucel.	Up to 1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Gunjan Shah, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Estimated): October 21, 2025
• Study Completion (Estimated): October 21, 2025

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Lymphoma; Memorial Sloan Kettering Cancer Center; N-Acetylcysteine; N-AC; CD19 CAR T-cell Therapy; 21-386
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 21-386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No